For the chemical synthesis of peptides, particularly, regarding the protection group for the amino group, 9-fluorenylmethoxy carbonyl group capable of disconnection under a weakly basic condition has attracted attention.
Heretofore, 9-fluorenylmethoxy carbonyl chloride has been known as a typical reaction reagent as the 9-fluorenylmethoxy carbonylation reagent. However, although this reagent is excellent in view of its reactivity, it has poor stability and requires use in excess amounts for the reaction to proceed, particularly, in an aqueous solution. In addition, it is stimulating and requires care upon handling. In order to overcome such problems, there have recently been developed active esters of 9-fluorenylmethoxy carbonylating reagents prepared by introducing an acyl amide portion to pentachlorophenol, p-nitrophenol, N-hydroxysuccinimide or active amide type acylating reagents represented by acyl imidazoles.
However, since these 9-fluorenylmethoxy carbonylating reagents have no water-solubility or hydrophilic property on the compound per se. Unfortunately, it is necessary to dissolve them in an organic solvent compatible with water, in the case of reaction in an aqueous solution, and then conduct the reaction with a substrate in the aqueous solution. Then, for recovering the reaction product, the organic solvent has to be distilled off from the reaction system.
Furthermore, since the removal of hydroxy compounds formed by the reaction is difficult, no satisfactory purity can be obtained, depending on the case, unless recrystallization or chromatographic purification is applied. Further, in the case of using those compounds instable in the organic solvent, for example, proteins or peptides as the substrate, the efficiency of the reaction is extremely reduced.